The mammalian urinary bladder represents a unique model for the study of the interrlationships between smooth muscle function and autonomic innervation. Although the parasympathetic (cholinergic) system is considered to be the primary system involved in micturition control, sympathetic innervatiin can modify and modulate bladder function. In addition, a third neurotransmitter system, possibly purinergic, may play an important role in normal bladder function. Alterations in hormonal levels can have marked effects on the innervation and response of the bladder to autonomic agonists. For these studies we will utilize a variety of in-vivo and in-vitro techniques including isolated smooth muscle baths, radioligand binding receptor assays, metabolic assays, and histochemical techniques. The specific aim of our study is to systematically determine the interrelationships between smooth muscle function (bladder) and autonomic innervation and determine the influence of hormones on both bladder and innervation. We expect to accomplish our specific aim through the following studies: 1) Determine the reciprocal influence of the adrenergic and cholinergic systems on bladder function. 2) Determine the contribution of the non-cholinergic, non-adrenergic innervation in normal bladder function. 3) Determine the characteristics of hormonal modification on bladder function and the effect of specific hormone administration on bladder innervation and response to autonomic agonists. The studies as outlined above should provide significant new information on both normal bladder function and the response of the bladder to specific neuronal and hormonal manipulations. The results of these studies should also provide significant clinically important informtion which can be applied directly to functional alterations in bladder function observed in a variety of bladder dysfunctions.